S-[alpha-(4-nitrobenzoyloxy)benzyl] o, o-diethyl phosphorodithioate



United States Patent Ofitice 3,168,436 Patented Feb. 2, 1965 3,168,436 S-[a-(4-NITROBENZOYLOXY)BENZYL](LO-DI- ETHYL PHUSPHORODITHIOATE John P. Chupp, Kirhwood, Mm, assignor to Monsanto Company, a corporation of Delaware No Drawing. Filed Apr. 7, 1960, Ser. No. 20,514-

2 Claims. (Cl. 16730) This invention relates to new and useful phosphorothioates and to methods of making same. Additionally this invention relates to insecticidal compositions containing the new phosphorothioates as an active ingredient.

The phosphorothioates of this invention can be represented by the structure wherein R and R are like or unlike lower alkyl radicals (i.e., methyl, ethyl, propyl, butyl, amyl, in the various isomeric forms thereof containing from 1 to 5 carbon atoms); wherein X is a chalkogen of atomic weight less than 40 (i.e., sulfur or oxygen); wherein A is hydrogen or phenyl, i.e., C H or an alkyl radical containing from 1 to 6 carbon atoms (e.g., methyl, ethyl, propyl, butyl, amyl, hexyl, and the various isomeric forms thereof); and wherein B is an organic radical directly attached by a carbon atom to the carbonyl carbon atom of the foregoing structure, containing from 1 to 7 carbon atoms and is free of non-benzenoid unsaturation, which radicals include open carbon atoms chain and closed carbon atom chain (i.e., ring) radicals free of olefinic and acetylenic unsaturation and include for example, aryl, alkaryl, aralkyl, alkyl, cycloalkyl, and like radicals containing from 1 to 7 carbon atoms which are substituted entirely by hydrogen atoms or substituted in Whole or in part by halogen atoms (i.e., those having an atomic number not higher than 35, e.g., chlorine, bromine and fluorine) or nitro groups. Typical of such groups are phenyl, 4-chlorophenyl, 3-chlorophenyl, 4-nitrophenyl, 3-nitrophenyl, 3, 4-dichlorophenyl, 3-chloro-4-nitrophenyl, 3,5-dinitrophenyl, 3,5 -dichlorophenyl, 2,4,5-trichlorophenyl, 4-bromophenyl, 4-iuorophenyl, 3-methylphenyl, 3-trifluoromethylphenyl, Z-methylphenyl, 4-methylphenyl, benzyl, 4-chlorobenzyl, 4-nitrobenzyl, cyclohexyl, 4 methylcyclohexyl, cyclopentyl, methyl, chloromethyl, ethyl, 2-chloromethyl, n-propyl, isopropyl, n-butyl, 3-chloro-n-butyl, isobutyl, n-amyl, isoamyl, n-hexyl isoheptyl, etc.

The phosphorothioates of this invention can be prepared by reacting in an anhydrous medium a salt (i.e., ammonium or alkali metal such as sodium, potassium or lithium) of a phosphorothioic acid of the structure PSH wherein R, R and X have the same significance as above with a substantially equimolecular amount of an ester of the structure wherein A and B have the same significance as above and wherein halogen means a halogen having an atomic number above 9 but not higher than 35 (i.e., chlorine or bromine, preferably chlorine) in the presence of an inert organic liquid or solvent (e.g., acetone, butanone, dioxane, chloroform, benzene, toluene, Xylene, etc.) While a wide range of reaction temperatures can be employed provided the system is fluid (i.e., a temperature above the freezing point of the system and up to and including the boiling point of the system) it is preferred to employ a reaction temperature in the range of 10 C. to 120 C.

As illustrative of the compounds of this invention is the following:

S-(benzoyloxymethyl) 0,0-dimethyl phosphorodithioate S-(benzoyloxymethyl) 0,0-diethyl phosphorothioate S-(benzoyloxymethyl) 0,0-diethyl phosphorodithioate S-(phenylacetyloxymethyl) 0,0-diethyl phosphorodithioate S- l- (benzoyloxy) ethyl] 0,0-dimethyl phosphorodithioate S[l-(benzoyloxy)isobutyl] 0,0-dimethyl phosphorothioate S-[a- (benzoyloxy) benzyl] 0,0-dimethyl phosphorodithioate S-[-ct(benzoyloxy)benzyl] 0,0-diethyl phosphorodithioate S- (acetyloxymethyl) 0,0-diisopropyl phosphorodithioate S4propionyloxymethyl) 0,0-diisobutyl phosphorothioate S- (propionyloxymethyl) 0,0-di-n-amyl phosphorodithioate S-(isobutyryloxymethyl) 0,0-di-n-propyl phosphorodithioate S- 1- (isobutyryloxy) ethyl] 0,0-dimethyl phosphorothioate S-(cyclohexylcarbonyloxymethyl) 0,0-dimethyl phosphorodithioate S-(4-chlorobenzoyloxymethyl) 0,0-dimethyl phosphorodithioate S-(4-chlorophenylacetyloxymethyl) 0,0-diethyl phosphorodithioate S-(4-nitrobenzoyloxymethyl) 0,0-diethyl phosphorodithioate S-(3,4-dichlorobenzoyloxymethyl) 0,0-dimethyl phosphorodithioate S-(3,5-dinitrobenzoyloxymethyl) 0,0-diethyl phosphorothioate S-(2,4-dichlorobenzoyloxymethyl) 0,0-dimethyl phosphorothioate S-(2,4,5-trichlorobenzoyloxymethyl) O-methyl O-ethyl phosphorothioate 1 S-(2,4,6-trichlorobenzoyloxymethyl) 0,0-diethyl phosphorothioate S-(2-chloro-4-nitrobenzcyloxymethyl) 0,0-diethyl phosphorothioate As illustrative of the preparation of the compounds of this invention is the following:

Example I To a suitable reaction vessel equipped with a thermometer, agitator and reflux condenser is charged approximately 13.0 parts by weight (substantially 0.065 mole) of ammonium 0,0-diethyl phosphorodithioate, approximately 10.0 parts by Weight (substantially 0.059 mole) of chloromethyl benzoate and approximately 88 parts'by weight of benzene. The mass is'heated at C. with agitation for 2 hours, cooled to room temperature and filtered. The filtrate is then washed with water and so-washed organic solution subjected to vacuum distillation to remove the benzene. The residue, an amber liquid, is S-(benzoyloxymethyl) 0,0-diethyl phosphorodithioate which is soluble in acetone, chloroform and ethyl alcohol but insoluble Employing the procedure of Example I but replacing To a suitable reaction vessel equipped with a thermometer, agitator and reflux condenser is charged approximately 30.0 parts by weight (substantially 0.16 mole) of ammonium 0,0-diethyl phosphorothioate, approximately 23.0 parts by weight (substantially 0.15 mole) of bromomethyl acetate, and approximately 80 parts by weight of acetone. The mass is then refluxed for 3 hours, cooled to room temperature and filtered. The filtrate is then subjected to vacuum distillation to remove the acetone. The residue is then taken up with methylene chloride and the organic solution washed with water. The so-washed organic solution is then subjected to vacuum distillation to remove the methylene chloride. The residue 32.3 parts by Weight of an amber liquid, is S-(acetyloxymethyl) 0,0- diethyl phosphorothioate which is soluble in benzene, chloroform and ethyl acetate but insoluble in water. Analysis.Theory: 12.8% P. Found: 12.7% P.

Example IV Employing the procedure of Example III but replacing bromomethyl acetate with an equimolar amount of 1- bromoethyl acetate there is obtained S-[l-(acetyloxy) ethyl] 0,0-diethyl phosphorothioate, an oil which is soluble in benzene but insoluble in water. Analysis.- Theory: 11.4% P. Found: 11.09% P.

Example V Employing the procedure of Example I but replacing ammonium 0,0-diethyl phosphorodithioate with an equimolar amount of ammonium 0,0-diethy1 phosphorothioate there is obtained S-(benzoyloxymethyl) 0,0-diethyl phosphorothioate, an amber liquid which is soluble in acetone, ethyl alcohol and ethyl acetate but insoluble in water. Analysis.Theory: 10.2% P. Found: 10.6% P.

Example I Example VII Employing the procedure of Example III but replacing bromomethyl acetate with an equimolar amount of 1- chloroethyl benzoate there is obtained S-[l-(benzoyloxy) ethyl] 0,0-diethyl phosphorothioate, an amber liquid, which is soluble in benzene, chloroform and ethyl acetate but insoluble in water. 'Analysis.Theory: 9.7% P, 10.1% S. Found: 93% P, 10.4% S.

Employing the procedure of Example III but replacing ammonium 0,0-diethyl phosphorothioate and bromomethyl acetate, respectively, with equimolar amounts of ammonium 0,0-diethyl phosphorodithioate and l-chloroethyl benzoate there is obtained as an amber liquid S- 0,0-diethyl phosphorothioate which is soluble in ethyl alcohol, chloroform and ethyl acetate but insoluble in water. Analysis.-Theory: 9.3%-P. Found: 9.0% P.

Example IX 0H5 Employing the procedure of Example III but replacing ammonium 0,0-diethyl phosphorothioate and bromomethyl acetate, respectively, with equimolar amounts of ammonium 0,0-diethyl phosphorodithioate and a-chlorobenzyl 4-nitrobenzoate there is obtained, in a 53 percent yield, S-[u-(4-nitrobenzoyloxy)benzyl] 0,0-diethyl phosphorodithioate an amber liquid, soluble in chloroform but insoluble in water.

Example X Employing the procedure'of Example III but replacing bromomethyl acetate with an equimolar amount of chloromethyl 4-chlorobenzoate there is obtained S-(4-chlorobenzoyloxymethyl) 0,0-diethyl phosphorothioate, an oil which is soluble in acetone methyl alcohol and chloroform but insoluble in water.

Example XI I Employing the procedure of Example I but replacing chloromethyl benzoate with an equimolecular amount of chloromethyl 4-chlorobenzoate there is obtained S-(4- chlorobenzoyloxymethyl) 0,0-diethyl phosphorodithioate, an oil, which is soluble in acetone, methyl alcohol and chloroform but insoluble in water.

The preferred phosphorothioates of this invention are those of the structure wherein R and R- are alkyl radicals containing from 1 to 2 carbon atoms; wherein X is a chalkogen of atomic weight less than 40 (i.e., sulfur or oxygen); wherein n is an integer from 0 to 1; and wherein B is a hydrocarbon radical containing from 1 to 7 carbon atoms and is free from non-benzenoid unsaturation. It is particularly preferred that B be phenyl i.e., C H

group of the ester reactant be chlorine.

The methods by which the phosphorothioates of this I invention are isolated will vary slightly with the reactants employed and the product produced. Further purification' by selective. solvent extraction or by absorptive agents such as activated carbon or clays can precede the removal of the inert organic liquid or solvent. Additionally an inert organic solvent can be added to and in the purification by absorptive agents. However, the product is generally satisfactory for insecticidal purposes without further purification.

It will be understood that the terms insect and insecticide are used herein in their broad common usage to include spiders, mites, ticks, and like pests which are not in the strict biological sense classed as insects. Thus, the usage herein conforms to the definitions provided by Congress in Public Law 104, the Federal Insecticide, Fungicide, and Rodenticide Act of 1947, Section 2, subsection h, wherein the term insect is used to refer not only to those small invertebrate animals belonging mostly to the class Insecta, comprising six-legged, usually winged forms, as beetles, bugs, bees, flies, and so forth, but also to other allied classes of arthropods whose members are Wingless and usually have more than six legs, as spiders, mites, ticks, centipedes, and wood lice.

The phosphorothioates of this invention are effective against a wide variety of insect pests. As illustrative of the activity but not limitative thereof is the following:

One gram of S-[l-(benzoyloxy) ethyl] 0,0-diethyl phosphorodithioate was dissolved in sufiicient acetone to make a concentrate solution thereof. Approximately 0.1 cc. of sorbitan monolaurate polyoxyethylene derivative (a commercial water-soluble non-ionic emulsifying agent) is then mixed with the concentrate. To this mixture and with agitation is added sufficient water to provide an aqueous emulsion having a concentration of 0.1% by weight of S-[l-(benzoyloxy)ethyl] 0,0-diethyl phosphorodithioate. Thereupon Lima bean plant leaves previously infested with the two spotted spider mite, Tetranychus telarius (L.), are dipped in the aqueous emulsion, withdrawn and set aside for observation. At the end of 48 hours a 100% kill of the mobile stage of the mite was noted. Seven days after setting the test specimen aside residual activity was confirmed, a 100% kill of both the resting stage and the ova stage being noted. Similar results against the mobile, resting and ova stages of the same mite were obtained employing S-(ac'etyloxymethyl) 0,0-diethyl phosphorodithioate instead of S-[l-(benzoyloxy)ethyl] 0,0-diethyl phosphorodithioate at the same concentration. In contrast, S-[Z-(acetyloxy) ethyl] 0,0-diethyl phosphorodithioate in the same test at a concentration of 0.2% by weight was inactive against the said mite.

Employing the following: S-(benzoyloxymethyl) 0,0-diethyl phosphorodithioate (the products of Example I),

S-(acetyloxymethyl) 0,0-diethyl phosphorothioate (the a 'phosphorothionate S-[a-(4-nitrobenzoyloxy)benzyl] 0,0-diethyl phosphorodithioate (the product of Example IX),

respectively, at a concentration of 0.001% by weight against yellow fever mosquito larvae, Ades aegypti, 100% kill in each instance .was observed.

Although the phosphorothioates of this invention are useful per se in controlling a wide variety of insect pests, it is preferable that they be supplied to the pests or to the environment of the pest or pests in a dispersed form in a suitable extending agent. i

In the instant specification it is to be understood that the term dispersed is usedin its widest possible sense. When it is said that the phosphorothioates of this invention are dispersed, it means that the particles of the phosphorothioates of this invention may be molecular in size and held in true solution in a suitable organic solvent. It means further, that the particles may be colloidal in size and distributed throughout a liquid phase in the form of suspensions or emulsions or in the form of particles held in suspension by wetting agents. It also includes particles which are distributed in a semi-solid viscous carrier such as petrolatum or soap or other oint-' Inent base in which they may be actually dissolved in the semi-solid or held in suspension in the semi-solid with the aid of suitable Wetting or emulsifying agents. The term dispersed also means that the particles may be mixed with and distributed throughout a solid carrier providing a mixture in particulate form, e.g., pellets, granules, powders, or dusts. The term dispersed also includes mixtures which are suitable for use as aerosols including solutions, suspensions, or emulsions of the phosphorothioates of this invention in a carrier such as dichloro-difluoromethane and like fluorochloroalkanes which boil below room temperature at atmospheric pressure.

In the instant specification it is to be understood that the expression extending agent includes any and all of those substances in which the phosphorothioates of this invention are dispersed. It includes, therefore, the solvents of a true solution, the liquid phase of suspensions, emulsions or aerosols, the semi-solid carrier of ointments and the solid phase of particulate solids, e.g., pellets, granules, dusts and powders.

The exact concentration of the phosphorothioates of this invention employed in combatting or controlling insect pests can vary considerably provided the required dosage (i.e., toxic or lethal amount) thereof is supplied to the pests or to the environment of the pests. When the extending agent is a liquid or mixture of liquids (e.g., as in solutions, suspensions, emulsions, or aerosols) the concentration of the phosphorothioate employed to sup ply the desired dosage generally will be in the range of 0.001 to 50 percent by weight. When the extending agent is a semi-solid or solid, the concentration of the phosphorothioate employed to supply the desired dosage generally will be in the range of 0.1 to 25 percent by weight. From a practical point of view, the manufacturer must supply the agriculturist with a low-cost concentrate or spray base or particulate solid base in such form that,

by merely mixingwith water or solid extender (e.g.,

powdered clay or talc) or other low-cost material available to the agriculturist atthe point of use, he will have an easily prepared insecticidal spray or particulate solid. In such a concentrate composition, the phosphorothioate generally will be present in a concentration of 5 to percent by weight, the residue being any one or more of the well-known insecticidal adjuvants, such as the various surface active agents (e.g., detergents, a soap or other emulsifying or wetting agent, surfaceactive clays), solvents,

diluents, carrier media, adhesives,;spreading agents; hu-

. mectants, and the like.

'S-[l-(acetyloxy)ethyl] 0,0-diethyl phosphorothioate (the product of Example IV), and

There are a large number of organic liquids which can be used for the preparation of solutions, suspensions, or emulsions of the phosphorothioates of this invention. For example, isopropyl ether, acetone, methyl ethyl ketone,

dioxane, cyclohexanone, carbon tetrachloride, ethylene dichloride, tetrachloroethane, hexane, heptane and like higher liquid alkanes, hydrogenated naphthalenes, solvent naphtha, benzene, toluene, xylene, petroleum fractions- (e.g., those boiling almost entirely under 400 F., at at mospheric pressure and having a flash point above about 80 particularly kerosene), mimeral oils having an unsulfonatable residue above about 80 percent and preferabl'y above about 90 percent. those instances where'- in there may be concern about the phytoxicity of the organic liquid extending agent a portion of same can be replaced by such low molecular weight aliphatic hydrocarbons as' dipentene, diisobutylene, propylene trime'r, and the like or suitable polar organic liquids such as the aliphatic ethers and the aliphatic ketones containing not more than about 10 carbon atoms as exemplified by acetone, methyl ethyl ketone, diisobutyl ketone, dioxa'ne, isopropyl ether, and the like. In certain instances, it is advantageous to employ a mixture of organic liquids as the extending agent.

When the phosphorothioates of this invention are to be supplied to the insect pests or to the environment of the pests as aerosols, it is convenient to dissolve them in a suitable solvent and disperse the resulting solution in dichlorodifluoromethane or like chlorofluoroalkanes which boils below room temperature at atmospheric pressure.

The phosphorothioates of this invention'are' preferably supplied to the insect pests or to'the environment of the insect pests in the form of emulsions or suspensions. Emulsions or suspensions are prepared by dispersing the phosphorothioate of this invention either per se or in the form of an organic solution thereof in water with the aid of a water-soluble surfactant. The term surfactant as employed here is used as in volume '11 of Schwartz, Perry and Berchs Surface Active Agents and Detergents (1958, Interscience Publishers, Inc., New York) in place of the expression emulsifying agent to connote generically the various emulsifying agents, dispersing agents, wetting agents and spreading agents that are adapted to be admixed with the active compounds ofthis invention in order to secure better Wetting and spreading of the active ingredients in the water vehicle or carrier in which they are insoluble through lowering the surface tension of the water (see also Fre'ar, Chemistry of Insecticides; Fungicides and Herbicides, second edition, page 280). These surfactants include the well-known capillary-active substances which may be anion-active (or anionic), cation active (or cationic), or non-ionizing (or non-ionic) which are described in detail in volumes I and II of Schwartz, Perry and Berchs Surface Active Agents and Detergents (1958, Interscience Publishers, Inc., New York) and also in the November 1947 issue of Chemical Industries (pages 811-824) in an article entitled Synthetic Detergents by John W. McCutcheon and also in the July, August, September and October 1952 issues of Soap and Sanitary Chemicals under the title Synthetic Detergents. The disclosures of these articles with respect to surfactants, i.e,, the anion active, cation-active and non-ionizing capillary active substances, are incorporated in this specification by reference in order to avoid unnecessary enlargement of this specification. The preferred surfactants are the water-soluble anionic surface-active agents and the water soluble non-ionic surface-active agents set forth in US. 2,846,398 (issued August 5, 1958). In general it is preferred that a mixture of water-soluble'anionic and water-soluble non-ionic surfactants be employed.

The phosphorothioates of this invention can be dispersed by suitable methods (e.g., tumbling or grinding) in solid extending agents either of organic or inorganic nature and supplied to the insect pest environment in particulate form. Such solid materials include for example, tricalcium phosphate, calcium carbonate, kaolin, bole, kieselguhr, talc, bentonite, fullers earth, pyrophyllite diatomaceous earth, calcined magnesia, volcanic ash, sulfur and the like inorganic solid materials, and include, for

intimate mixture of phosphorothioates of this invention ticularlymites) by the addition of water thereto.

example, such materials of. organic nature as powdered cork, powdered wood, and powdered walnut shells. The

preferred solid carriers are the adsorbent clays, e.g., bentonite. These mixtures can be used for insecticidal purposes in the dry form, or, by addition ofwater-soluble surfactants or wetting agents the dry particulate solids can be rendered wettable by water so as .to obtain stable aqueous dispersions, or suspensions suitable for use as sprays.

For special purposes the phosphorothioates of this invention can be dispersed in a semi-solid extending agent such as petrolatum or soap (e.g., sodium stearate or oleate or palmitate or mixtures thereof) with or without the aid of solubility 'promotors and/or surfactants or dispersing agents.

In all of the forms described above the dispersions can be provided ready for use in combatting insect pests or they can be provided in a concentrated form suitable for mixing with or dispersing in other extending agents. As illustrative of a particularly useful concentrate is an with a water-soluble surfactant which lowers the surface tension of water in the Weight proportions of 0.1 to 15 parts of surfactant with sufficient of the phosphorothioate of this invention to make 100 parts by weight. Such a concentrate 'is particularly adapted to be made into a spray for combatting various forms of insect pests (par- As illustrative of such a concentrate is an intimate mixture of parts by weight of S-[1-(benzoyloxy)ethyl] 0,0- diethyl phosphorodithioate and 5 parts by weight of a water-soluble non-ionic surfactant such as the polyoxyethylene derivative or sorbitan monolaurate.

Another useful concentrate adapted to be made into a spray for combatting insect pests (particularly mites) is a solution (preferably as concentrated as possible) of a phosphorothioate of this invention in an organic solvent therefor. The said liquid concentrate preferably contains dissolved therein a minor amount (e.g., 0.5 to 10 percent by weight of the Weight of the new insecticidal agent) of a surfactant (or emulsifying agent), which surfactant is also water-soluble. As illustrative of such a concentrate is a solution of S-(benzoyloxymethyl) 0,0- diethyl phosphorodithioate in benzene which solution contains dissolved therein a water-soluble polyoxyethylene glycol non-ionic surfactant and a water-soluble alkylaryl sulfonate anionic surfactant.

Of the surfactants aforementioned in preparing the var ious emulsifiable, wettable or dispersible compositions or concentrates of this invention, the anionic and non-ionic surfactants are preferred. Of the anionic surfactants, the particularly preferred are the well-known water-soluble alkali metal alkylaryl sulfonates as exemplified by sodium decylbenzene sulfonate and sodium dodecylbenzene sulfonate. Of the non-ionic surfactants, the particularly preferred are the water-soluble polyoxyethylene derivatives of alkylphenols (particularly isooctylphenol) and the water-soluble polyoxyethylene derivatives of the mono-higher fatty acid esters of hexitol anhydrides such as mannitan or sorbitan.

In all of the various dispersions described hereinbefore for insecticidal purposes, the active ingredients can be one 'or more of the compounds of this invention. The compounds of this invention can also be advantageously employed in combination with other pesticides, includtional fashion which permits contact between the insect pests and the phosphorothioates of this invention. Such dispersing can be brought about by applying the phosphorothioates per se or sprays or particulate solid compositions containing same to a surface infested with the insect pests or attractable to the pests, as for example, the surface of agricultural soil or other media such as the above ground surface of plants by any of the conventional methods, e.g., power dusters, boom and hand sprayers, and spray duster-s. Also for sub-surface application such dispersing can be carried out by simply mixing the new insecticidal agent per se or insecticidal spray or particulate solid compositions comprising same with the infested environment or with the environment the insect pests frequent, or by employing aliquid carrier for the new insecticidal agent to accomplish sub-surface penetration and impregnation therein.

While this invention has been described with respect to certain embodiments, it is to be understood that it is not so limited and the variations and modifications thereof obvious to those skilled in the art can be made without departing from the spirit and scope thereof.

What is claimed is: 1.

2. The method of controlling insects which comprises contacting the insects with a toxic amount of the compound of claim 1.

References Cited in the file of this patent UNITED STATES PATENTS 2,862,019 Schrader Nov. 25, 1958 2,909,559 Lanham Oct. 20, 1959 2,915,429 Scherer Dec. 1, 1959 2,920,993 Fairchild Jan. 12, 1960 2,931,825 Lutz Apr. 5, 1960 2,945,053 McConnell et a1. July 12, 1960 OTHER REFERENCES Gar et al.: Chem. Abst., vol. 48, col. 6639 (1954).

Paikin et al.: Chem. Abst., vol. 52, col. 4096-4097 (1958).

Rossi et al.: La Chimica e lIndustria, 42, p. 238

' (March 1960). 

